There appears to be a strong association between magnesium deficiency and insulin resistance. Supplementation in individuals with the metabolic syndrome could improve insulin sensitivity and prevent or delay the onset of type 2 diabetes mellitus and its complications. Though a number of researchers have reported an association between magnesium intake and risk of diabetes mellitus, metabolic syndrome, and/or insulin resistance, only two studies to date have administered magnesium supplementation in a randomized, placebo-controlled trial (RCT). In addition, the two RCTs were conducted in Mexico, limiting their generalizability among a more diverse population, such as that in the U.S. Furthermore, these studies were only 12 and 16 weeks, respectively, and the researchers did not conduct follow-up analyses to assess adherence to the supplementation and/or possible long-term effects of the supplementation. At present, there have been no RCT's of magnesium supplementation in individuals with the metabolic syndrome. Based on these data, we will assess the effectiveness of magnesium supplementation in a six-month, randomized, double-blind placebo-controlled trial on insulin sensitivity in obese African American and Caucasian individuals with the metabolic syndrome relative to a placebo. Participants will be randomized to either 350 mg (14.6 mmol) of elemental magnesium per day, provided as magnesium chloride or placebo. Our aims will be to: 1) evaluate insulin resistance using frequently sampled intravenous glucose tolerance test (FSIVGTT) and homeostasis model assessment of insulin resistance index (HOMA-IR), and 2) assess the effect of magnesium supplementation on serum glucose concentrations, serum lipid levels (serum total cholesterol, serum low density lipoprotein cholesterol [LDL-C], serum high density lipoprotein cholesterol [HDL-C], and serum triglyceride concentrations), C-reactive protein levels, and blood pressure in individuals with the metabolic syndrome relative to a placebo. If magnesium supplementation is successful in improving insulin sensitivity, individuals with the metabolic syndrome would have less expensive, safe choice to prevent or delay the onset of type 2 diabetes mellitus. Because obesity and subsequently, type 2 diabetes mellitus, are increasing in prevalence, this research could have strong effect on the public health of our nation. PUBLIC HEALTH RELEVANCE: Many people consume processed foods, leading to decreased consumption of important micronutrients, such as magnesium; these same individuals might be adherent to magnesium supplementation, even though dietary change is more challenging. With the significance of the problem of type 2 diabetes mellitus and its link to the obesity epidemic, any simple method of disease mitigation deserves serious examination. If effective in improving insulin resistance in the metabolic syndrome, magnesium supplementation could have a great public health impact by delaying or preventing type 2 diabetes mellitus, and also in decreasing health care costs. [unreadable] [unreadable] [unreadable]